ICDD Powder Diffraction File Coverage of Polymers Used in Pharmaceutical and Biomedical Applications

T. BLANTON, S . GATES-REC TOR, T. FAWCET T, ICDD

S. MISTURE, ALFRED UNIVERS ITY

This document was presented at PPXRD -Pharmaceutical Powder X-ray Diffraction Symposium

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What is a polymer?The word polymer is derived from the Greek words polus, meaning many, and meros, meaning parts.

A long-chained molecule that is composed of individual units, called monomers.

A compound typically of high molecular weight derived either by the addition of many smaller molecules, such as polyethylene, or by the condensation of many smaller molecules with the elimination of water, alcohol, or the like, such as nylon.

Polymers can be natural or synthetic

There are inorganic polymer and coordination polymer materials, we will focus on carbon or silicone based polymers

Polymer analysis using XRDMany techniques are used for polymer characterization◦ IR, NMR, GC/MS, etc.

Why use XRD?◦ Polymers can have amorphous and crystalline regions ◦ Crystallite size is small and measurable by XRD◦ Polymers are often used as the base component in pharmaceutical and biomedical composite materials

Highly crystalline - Teflon

Semi crystalline – polyethylene terephthalate

Micro crystalline – cellulose 1β

Amorphous - polycarbonate

Polymer order:

XRD pattern for atactic polystyrene –effect of the polymer chain structure

Inter-chain

Side-group

Intra-molecular

Inter

Intra

Side

Effect of tacticity on polymer order

Atactic PSIsotactic PS

iPS

aPS

Rhombohedral R-3ca=22.049ÅC=6.723Å

CastNo heatsetNo stretch

Heatset120 °C, 10sNo stretch

Heatset6XUniax stretch

Bragg Brentano Reflection Mode XRD Patterns - Effect of Processing on Polypropylene

CastNo heatsetNo stretch

Heatset120 °C, 10sNo stretch

Heatset6XUniax stretch

2-D transmission XRD patterns - Effect of processing and sample orientation on polypropylene XRD patterns

Pharmaceuticals

Shell from an Allegra tablet

Biomedical devices

Transdermal patch backing

Powder Diffraction File PDF Polymer Entry – PEEK Polymer

Powder Diffraction File PDF Polymer Entry – PEEK Polymer

PD3 Raw Data Patterns in the Powder Diffraction File – PEEK Polymer

Traditional d,I stick pattern PD3 raw data pattern

Simulated/stick pattern Semicrystalline

Orthorhombic Pbcna=7.831Å b=5.891Å c=9.958Å

PD3 Raw Data Patterns in the Powder Diffraction File – PEEK Polymer

Amorphous

• PVOH 110K Mw raw data (red)• PVOH 50Å simulated pattern (blue)• PVOH d,I stick pattern (black)

Stick vs. Simulated vs. PD3 (PVOH – tablet packaging)

Polymer entries in PDF 2015

PD3 polymer entries in PDF 2015

With PD3 raw data

ICDDpharmaceutical polymers project

Polymer Mol. Formula PDF Entry PD3poly(acrylic acid), PAA (C3H4O2)n N Npoly(ethylene oxide), PEO (C2H4O)n Y Npoly(ethylene glycol), PEG (C2H4O)n Y Npoly(vinyl pyrrolidone), PVP (C6H9NO)n N Npoly(vinyl alcohol), PVOH, PVA (C2H4O)n Y Ypolyacrylamide, PAM (C3H5NO)n N Npoly(N-isopropylacrylamide) (C6H11NO)n N Ncellulose (C6H10O5)n Y Ymethyl cellulose (C6H7O5R1, 2, 3)n R=CH3 Y Yethyl cellulose ((C6H8O5(C2H5)2)n N Ncarboxymethyl cellulose (C6H7O5R1, 2, or 3)n R=H or CH2CO2H N Nhydroxyethyl cellulose (C6H7O5R1, 2, or 3)n R=H or CH2CH2OH N Nhydroxypropyl cellulose (C6H7O5R1,2, or 3)n R=H or CH2CH(OH)CH3 N Nhydroxypropyl methyl cellulose, HPMC (C6H7O5R1,2, or 3)n R=H or CH3 or CH2CH(OH)CH3 N Ncellulose acetate phthalate (C6H7O5R1,2, or 3)n R=H or CH3CO or C6H4COCOOH Y Yalginic acid (C6H8O6)n N Nchitosan (C6H11O4N)n Y Nhyaluronic acid (C14H21NO11)n N Npectinic acid (C13H14O13)n N Npoly(lactide-co-glycolic acid, PLGA) (C3H4O2)m(C2H2O2)n N Nstarch (C6H10O5)n Y N

sodium starch glycolate (C2H4O3Na)n N Ndextran H(C6H10O5)nOH Y Yxanthum Gum C35H49O29 (monomer) N Ngelatin (C35H55N12O12)n Y Y

ICDD biomedicalpolymers

Polymer Mol. Formula PDF Entry PD3polyurethane, PU (R-NHCO2)n Y N

silicone (OSiR2)n Y N

polycarbonate, PC (ROCO2)n Y Y

polychloroprene (C4H5Cl)n Y Npolyisobutylene, PIB (CH2C(CH3)2)n Y Npolycyanoacrylate (C5H5O2N)n N N

poly(vinyl acetate), PVAc (C4H6O2)n N N

polystyrene, PS atactic (C8H8)n Y Y

polystyrene, PS isotactic (C8H8)n Y N

polypropylene, PP (C3H6)n Y Y

poly(vinyl chloride), PVC (C2H3Cl)n Y Y

polyethylene (C2H4)n Y Y

poly (methyl methacrylate) (C5H8O2)n Y N

poly(hydroxyethyl methacrylate) (C6H10O3)n N N

Ethylene vinyl acetate, EVA (C2H4)m(CC4H6O2)n Y Y

poly(ethylene terephthalate, PET (C10H8O4)n Y Y

polyether ether ketone (OC6H4OC6H4COC6H4)n N N

2016 PDF-4 new polymer entries (PHR, BIO subfiles)

Phase ID – Ag based antimicrobial hospital gown

Backscattered SEM

Ag2SO4 compounded in polypropylene was analyzed for phase composition. Using PDF-4 tools, phases were identified. Phases present: α-polypropylene (base polymer), Ag2SO4 (antimicrobial agent), Ag0 (Ag2SO4 reduced

during compounding), and montmorillonite (clay for improving polymer physical properties)

Do you need multiple Entries in the PDF Database for a polymer?

∆

ε

AmorphousPET

Thermally crystallizedPET

Strain crystallizedPET

PETTriclinic P-1a=5.791Å b=9.040Å c=4.561Åα=100.64° β=112.46° γ=75.93°

Polymer diffraction pattern: sample orientation mattersStrain crystallized PET

B-B diffractometerReflection mode

B-B diffractometerTransmission mode

Quantitative Phase Analysis PET Composite Film

Composite used for transdermal patch backing. XRD phase analysis identified biaxially oriented poly(ethylene terephthalate) (PDF 00-061-1413) and TiO2-anatase (00-021-1272). Since the biaxially oriented PET raw data pattern is stored in the PDF, whole pattern fitting can be used for quantitative analysis. WPF finds 1.3wt% TiO2 present, in line with the formulation calling for 1.5wt% TiO2.

Cellulose

Amorphous

Iβ II

Monoclinic P21a=8.260Å b=10.388Å c=7.740Åβ=95.80°

Monoclinic P21a=9.044Å b=10.387Å c=8.077Åβ=115.73°

Phase identification – Allegra® shell

amorphous, Iβ – celluloseHydroxypropyl methyl

celluloseMg Stearate 2H2OStearic acidAnatase TiO2

α,β – mannitol

Poly Lactic Acid PLA

Annealed 90 °C L-PLA α´ phaseorthorhombic

a=10.835Åb=6.198Å

c=28.951Å

Annealed 140 °C L-PLA α phaseorthorhombic

a=10.653Åb=6.313Åc=28.81Å

Melt-quenchamorphous L-PLA

Melt-quenchamorphous 98/12 L/D-PLA

3d printing polymers, continued

Polycarbonate Acrylonitrile butadiene styrene

Polyvinyl alcohol2K mol. wt.78% hydrolyzed

110K mol. wt.99% hydrolyzed

110K mol. wt.99% hydrolyzed Thermally crystallized

Monoclinica=7.773Å b=2.538Å c=5.502Åβ=92.11°

Cellulose triacetate IAmorphous

Thermally crystallizedMonoclinic P21a=11.348Å b=24.690Å c=6.060Åβ=95.60°

Cellulose triacetate IIAmorphous

Oriented film Thermally crystallizedfilm Orthorhombic P212121

a=11.530Å b=24.690Å c=10.540Å

Methyl cellulose

Thermally crystallized

Amorphous

Orthorhombica=10.435Å b=43.140Å c=4.633Å

Ethyl cellulose – new entry for 2016

Ethyl cellulose

As received

200 °C 30 min

Indexing/WPF of crystalline “ethyl cellulose” phase

Possible cell:MonoclinicSG P21/ca=11.74Åb=23.50Åc=7.65Åβ=95.2°

Collecting supporting data:TGA/DSC, NMR, IR, XRF, SEM

Ethyl cellulose – isothermal anneal studies190 °C

Ethyl cellulose – isothermal anneal studies

Summary

• Raw data diffraction patterns generated from analysis of polymer samples are being added to ICDD PDF-4 databases

• Important considerations:• Polymer chemistry• Polymer processing• Sample orientation in diffractometer - reflection vs. transmission • Sample type (powder, film, fiber)

• Use caution when using a single peak amorphous pattern to define the amorphous phase• Pay attention to sample prep

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